異位性皮膚炎(atopic dermatitis, AD)是一種反覆發作的皮膚疾病，常見於嬰幼兒期，主要症狀為反覆搔癢、皮膚紅腫、乾燥、溼疹等。免疫功能異常是主要導致異位性皮膚炎的原因，而氧化壓力過高也會導致其症狀的惡化。多酚類藥物對於抗氧化與抗發炎皆有顯著的效果，具有治療異位性皮膚炎的潛力。本研究利用每日塗抹低(100 μg/day)與高(200 μg/day)劑量薑黃素(curcumin, CUR)溶液於異位性皮膚炎小鼠持續4週，發現高低劑量組之皮膚炎分數分別可從4分降至1.5與1分，證實薑黃素之治療有效性。為了提高給藥效率與與減少給藥頻率，本研究以聚乳酸－羥基乙酸共聚物[poly(lactic-co-glycolic acid), PLGA]包覆疏水性多酚類藥物薑黃素，並結合玻尿酸(hyaluronic acid, HA)包覆親水性多酚類藥物沒食子酸(gallic acid, GA)製作成雙層式微針。當微針穿刺時，後端水溶性HA可在5分鐘內溶解並釋放出GA，而前端PLGA可鑲嵌至皮膚內達到緩速釋放的效果，穿刺深度約550 μm，且傷口可在54小時內恢復完畢。每片微針包覆225 ± 19 μg (n = 8)的薑黃素與117 ± 10 μg (n = 5)的GA，且可以持續釋放薑黃素長達63天，而GA也可持續釋放11天。施打2片包覆薑黃素微針(CUR MN)或2片包覆薑黃素與GA微針(CUR/GA MN)於異位性皮膚炎Nc/Nga小鼠上，8週後皆可有效改善皮膚炎症狀。其中CUR/GA MN組分數可以從4.5分降至1.6分，優於CUR MN組(從4.5分降至3分)，並能改善表皮增厚與肥大細胞浸潤情形、抑制血中IgE與組織胺以及皮膚中Th1與Th2相關細胞激素，同時降低皮膚中活性氧分子含量以減緩發炎症狀。以上研究證實，施打一次CUR/GA MN即可長期且有效地改善異位性皮膚炎症狀，有潛力成為未來異位性皮膚炎的新療法。

In this study, curcumin (CUR), a hydrophobic polyphenol, was administrated topically on DNCB-induced Nc/Nga mice to find the theurepetic dosage for atopic dermatitis (AD) treatment. Results showed that the symptoms of AD and serum IgE level can be alleviated with the dosage of 100 μg/day of curcumin after 4-week treatment. Based on this dosage, a double-layered [poly(lactic-co-glycolic acid), PLGA]/(hyaluronic acid, HA) microneedles (MNs) was fabricated. After applying MNs for 5 min, HA can quickly dissolve, then PLGA tip can be embedded into skin for sustained release of CUR up to 63 days. In order to increase the amount of drug at early treatment, a hydrophilic polyphenol gallic acid (GA) was loaded by HA. With the rapid dissolve of HA, GA can be retained in the skin for at least 8 days. MN-created microchannels can be recovered within 54 h. After the insertion of 2 patches of CUR loaded-MNs (CUR MN), or CUR and GA loaded-MNs (CUR/GA MN) into AD-like Nc/Nga mice, the SCORAD index can be declined after 8-week treatment, from 4.5 to 3 and 1.6 respectively, indicating that CUR/GA MN group has better therapeutic effect than CUR MN group. AD symptoms, serum IgE and histamine levels as well as Th1-associated cytokine (IFN-γ), Th2-associated cytokines (IL-4, IL-5 and IL-13) and reactive oxygen species (ROS) in tissue were all inhibited after MN treatment. Compared with daily topical treatment of AD, CUR/GA MN provided a sustained release of CUR up to 2 months, which has potential therapeutic effect for future AD treatment.

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